Current practices in nutrition management and disease incidence of common marmosets (Callithrix jacchus).

Background: A survey was developed to characterize disease incidence, common pathology lesions, environmental characteristics, and nutrition programs within captive research marmoset colonies.

Methods: Seventeen research facilities completed the electronic survey.

Results: Nutritional management programs varied amongst research institutions housing marmosets; eight primary base diets were reported.

Trial-to-trial, uncertainty-based adjustment of decision boundaries in visual categorization.

Categorization is a cornerstone of perception and cognition. Computationally, categorization amounts to applying decision boundaries in the space of stimulus features. We designed a visual categorization task in which optimal performance requires observers to incorporate trial-to-trial knowledge of the level of sensory uncertainty when setting their decision boundaries.

Phosphotyrosyl peptides block Stat3-mediated DNA binding activity, gene regulation, and cell transformation.

Signal transducers and activators of transcription (STATs) comprise a family of cytoplasmic signaling proteins that participates in normal cellular responses to cytokines and growth factors. Frequently, however, constitutive activation of certain STAT family members, particularly Stat3, has accompanied a wide variety of human malignancies. To identify small molecule inhibitors of Stat3, we investigated the ability of the Stat3 SH2 domain-binding peptide, PY*LKTK (where Y* represents phosphotyrosine), to disrupt Stat3 activity in vitro.

Constitutive activation of Stat3 by the Src and JAK tyrosine kinases participates in growth regulation of human breast carcinoma cells.

Constitutive activation of signal transducer and activator of transcription (STAT) proteins has been detected in a wide variety of human primary tumor specimens and tumor cell lines including blood malignancies, head and neck cancer, and breast cancer. We have previously demonstrated a high frequency of Stat3 DNA-binding activity that is constitutively-induced by an unknown mechanism in human breast cancer cell lines possessing elevated EGF receptor (EGF-R) and c-Src kinase activities. Using tyrosine kinase selective inhibitors, we show here that Src and JAK family tyrosine kinases cooperate to mediate constitutive Stat3 activation in the absence of EGF stimulation in model human breast cancer cell lines.

Accessibility of the c-Src SH2-domain for binding is increased during mitosis.

The Src homology 2 (SH2) region is a noncatalytic domain of Src-family tyrosine kinases and other proteins which participants in inter- and intramolecular interactions of tyrosine-phosphorylated proteins. A synthetic peptide modeled on the c-Src carboxyl terminus, which contains phosphotyrosine at position 527, binds recombinant SH2 and the SH2-domain of c-Src which lacks phosphotyrosine 527. Unphosphorylated peptide does not bind detectably.

Regulation of c-Src tyrosine kinase activity by the Src SH2 domain.

The protein-tyrosine kinase activity of pp60c-src (c-Src) is inhibited by phosphorylation of tyr527, within the c-Src c-terminal tail. Genetic and biochemical data have suggested that this negative regulation requires an intact Src homology 2 (SH2) domain. Since SH2 domains recognize phosphotyrosine, it is possible that these two non-catalytic domains associate, and thereby repress c-Src kinase activity.

Antiserum raised against a synthetic phosphotyrosine-containing peptide selectively recognizes p185neu/erbB-2 and the epidermal growth factor receptor.

Rabbits were immunized with a synthetic phosphopeptide corresponding to a major autophosphorylation site of p185neu/erbB2 to determine the feasibility of producing tyrosine-phosphopeptide-specific antibodies. A series of adsorption and affinity chromatography steps were used to select antibodies with the desired reactivity. Immunoblot experiments showed that the resulting serum is highly specific for tyrosine-phosphorylated forms of p185 and the related epidermal growth factor receptor.

Glucose repression of the yeast ADH2 gene occurs through multiple mechanisms, including control of the protein synthesis of its transcriptional activator, ADR1.

The rate of ADH2 transcription increases dramatically when Saccharomyces cerevisiae cells are shifted from glucose to ethanol growth conditions. Since ADH2 expression under glucose growth conditions is strictly dependent on the dosage of the transcriptional activator ADR1, we investigated the possibility that regulation of the rate of ADR1 protein synthesis plays a role in controlling ADR1 activation of ADH2 transcription. We found that the rate of ADR1 protein synthesis increased 10- to 16-fold within 40 to 60 min after glucose depletion, coterminous with initiation of ADH2 transcription.

Developmental regulation of transmembrane signaling via the T cell antigen receptor/CD3 complex in human T lymphocytes.

We have examined transmembrane signaling events via the TCR/CD3 complex (TCR/CD3) at various stages of T cell development for evidence of developmental regulation. Engagement of TCR/CD3 induced defective activation of phospholipase C (PLC) in thymocytes relative to peripheral blood T lymphocytes. The defect in PLC activation via TCR/CD3 was restricted to immature thymocytes (CD3low, CD4+CD8+).

Phosphorylation occurs in the amino terminus of the Raf-1 protein.

The ability of the Raf-1 protein to morphologically transform murine fibroblasts can be activated by amino-terminal deletions or substitutions. We have compared the phosphorylation states of full-length and representative transforming and non-transforming amino-terminal deletion mutants of the Raf-1 protein using phosphoamino acid analysis and tryptic phosphopeptide mapping. Several [32P]orthophosphate-labeled tryptic phosphopeptides that were present in the full-length Raf-1 protein were absent from the highly transforming 22W Raf-1 mutant (lacking 305 amino-terminal residues).

Impairment of counterregulatory hormone responses to hypoglycemia in pregnant women with insulin-dependent diabetes mellitus.

Intensive insulin therapy directed at elimination of hyperglycemia is advocated during pregnancy in women with insulin-dependent diabetes mellitus. Because such treatment is complicated by frequent hypoglycemic episodes, we evaluated maternal and fetal responses in nine intensively treated pregnant women with insulin-dependent diabetes mellitus during an insulin-induced, gradual, controlled fall in plasma glucose levels. In contrast to values in nonpregnant control women, reductions in glucose to 44 +/- 2 mg/dl in pregnant diabetic patients failed to elicit an increase in glucagon levels.

Selective binding of activated pp60c-src by an immobilized synthetic phosphopeptide modeled on the carboxyl terminus of pp60c-src.

Phosphorylation of the carboxyl terminus of pp60c-src, the product of the c-src protooncogene, at Tyr-527 suppresses its tyrosine kinase activity and transforming potential. It has been proposed that the phosphorylated carboxyl terminus of pp60c-src inhibits kinase activity by binding to the SH2 (src homology 2) domain. We have synthesized peptides corresponding to the carboxyl-terminal 13 residues of pp60c-src phosphorylated and nonphosphorylated at Tyr-527.

Effect of acute physiological elevations of insulin on circulating androgen levels in nonobese women.

Extreme pharmacological elevation of the circulating insulin level acutely lowers dehydroepiandrosterone sulfate (DHEAS) levels. To assess whether more physiological elevations in plasma insulin (due to exogenous infusion or endogenous secretion) would have similar effects, we examined the levels of DHEAS, androstenedione, testosterone, and free testosterone before and after euglycemic hyperinsulinemic and hyperglycemic hyperinsulinemic clamp studies. Studies were performed in women within 20% of ideal body weight after an overnight fast.

In vivo phosphorylation and membrane association of the fyn proto-oncogene product in IM-9 human lymphoblasts.

The protein product of the src-related proto-oncogene, fyn, was isolated from IM-9 cells with antibodies specific for the amino-terminal 22 residues of the fyn protein. Peptide mapping demonstrated that the fyn protein was distinct from the closely related c-src and c-fgr proteins. The fyn protein from IM-9 cells incorporated [3H]myristate in vivo and was found to be membrane associated.

Structural requirements of iron-responsive elements for binding of the protein involved in both transferrin receptor and ferritin mRNA post-transcriptional regulation.

The synthesis of both transferrin receptor (TfR) and ferritin is regulated post-transcriptionally by iron. This is mediated by iron responsive elements (IREs) in the 5'- and 3'-untranslated regions, respectively, of TfR and ferritin mRNAs. Although these IREs have different sequences, they both form a characteristic stem-loop.

Definition of the human raf amino-terminal regulatory region by deletion mutagenesis.

Activation of transforming potential of the cellular raf gene has uniformly been associated with the deletion of amino-terminal coding sequences. In order to determine whether 5' truncation alone could activate cellular raf, we constructed 21 human c-raf-1 cDNAs with variable BAL 31-generated deletions distal to a Moloney murine sarcoma virus long terminal repeat and a consensus translation initiation sequence. The deletions ranged from 136 to 1,399 nucleotides of coding sequence and shortened the 648-amino-acid raf protein by 44 to 465 amino acids.

Cloning and sequencing of a cDNA encoding DNA methyltransferase of mouse cells. The carboxyl-terminal domain of the mammalian enzymes is related to bacterial restriction methyltransferases.

A cDNA encoding DNA (cytosine-5)-methyltransferase (DNA MeTase) of mouse cells has been cloned and sequenced. The nucleotide sequence contains an open reading frame sufficient to encode a polypeptide of 1573 amino acid residues, which is close to the apparent size of the largest species of DNA MeTase found in mouse cells. The carboxylterminal 570 amino acid residues of the inferred protein sequence shows striking similarities to bacterial type II DNA cytosine methyltransferases and appears to represent a catalytic methyltransferase domain.

Phosphorylation of tyrosine in the carboxyl-terminal tryptic peptide of pp60c-src.

The major site of tyrosine phosphorylation of the transforming protein of Rous sarcoma virus, pp60v-src (tyrosine-416), is different from the major site of tyrosine phosphorylation of its nontransforming normal cellular counterpart, pp60c-src. We have shown that antibodies against a synthetic peptide modeled on the carboxyl-terminal 13 residues of pp60c-src specifically immunoprecipitate the major phosphotyrosine tryptic peptide of pp60c-src from both chicken and rat fibroblasts. These experiments localize the major site of tyrosine phosphorylation to one or more of the three tyrosine residues in the carboxyl-terminal tryptic peptide at positions 511, 519, and 527 of the amino acid sequence of chicken pp60c-src.

Influence of calcium ion on the binding of fibrin amino terminal peptides to fibrinogen.

The affinity of the amino terminal tetrapeptide of the beta chain of fibrin, Gly-His-Arg-Pro, for fibrinogen dramatically increases in the presence of 2 millimolar calcium ion. In contrast, there is no significant increase in the affinity of peptides beginning with the amino terminal sequence of the fibrin alpha chain, Gly-Pro-Arg, in the presence of calcium ions, although the number of binding sites increases. In the latter case, the increased number of sites is due to the alpha chain analogs binding to the site ordinarily occupied by the beta chain analogs.

Antibodies specific for the carboxy- and amino-terminal regions of simian virus 40 large tumor antigen.

Antibodies specific for the amino- and carboxy-terminal portions of simian virus 40 large tumor (T) antigen were obtained by immunization of rabbits with synthetic peptides corresponding to these regions. The amino-terminal synthetic peptide has the sequence Ac-Met-Asp-Lys-Val-Leu-Asn-Arg-(Tyr). The tyrosine residue was introduced in order to couple the peptide to bovine serum albumin with bis-diazotized benzidine.

Synthetic peptide derivatives that bind to fibrinogen and prevent the polymerization of fibrin monomers.

A series of small peptides corresponding to the amino termini of the fibrin alpha- and beta-chains has been synthesized. The peptides glycyl-L-prolyl-L-arginyl-L-proline and glycyl-L-prolyl-L-arginylsarcosine are potent inhibitors of fibrin polymerization. Moreover, these peptides have a natural stability stemming from their inherent resistance to proteolysis because of the involvement of amino acids in each of their peptide bonds.